Identification of a Small Molecule Compound Active against Antibiotic-Tolerant Staphylococcus aureus by Boosting ATP Synthesis.

Antibiotic tolerance poses a threat to current antimicrobial armamentarium. Bacteria at a tolerant state survive in the presence of antibiotic treatment and account for persistence, relapse and recalcitrance of infections. Antibiotic treatment failure may occur due to antibiotic tolerance. Persistent infections are difficult to treat and are often associated with poor prognosis, imposing an enormous burden on the healthcare system. Effective strategies targeting antibiotic-tolerant bacteria are therefore highly warranted. In this study, small molecule compound SA-558 was identified to be effective against Staphylococcus aureus that are tolerant to being killed by conventional antibiotics. SA-558 mediated electroneutral transport across the membrane and led to increased ATP and ROS generation, resulting in a reduction of the population of antibiotic-tolerant bacteria. In a murine chronic infection model, of which vancomycin treatment failed, we demonstrated that SA-558 alone and in combination with vancomycin caused significant reduction of MRSA abundance. Our results indicate that SA-558 monotherapy or combinatorial therapy with vancomycin is an option for managing persistent S. aureus bacteremia infection and corroborate that bacterial metabolism is an important target for counteracting antibiotic tolerance.

Conformational Free-Energy Differences of Large Solvated Systems with the Focused Confinement Method.

The focused confinement method (FCM) is a reaction coordinate-free simulation approach for the calculation of conformational free-energy differences in explicit solvent. The method uses reference states for the conformations of interest, partitions the solute into conformationally active and inactive regions, and requires the calculation of desolvation free energies of mixed harmonic-anharmonic states as part of its procedure. The reference states and partitioning affect the speed of convergence of FCM's constituent simulations in opposing manners, but in the thermodynamic limit, they have no effect on calculated conformational free-energy differences. To aid fast convergence of large systems, a general procedure to quickly partition and construct reference states is introduced. With this, two sets of reference states and associated partitionings were constructed for the closed and open conformation of triosephosphate isomerase (TIM). Despite TIM's size, highly converged desolvation free energies were readily obtained from standard free-energy perturbation simulations because the mixed harmonic-anharmonic states are heavily rigidified. FCM-calculated free-energy differences for loop closing matched the experimental value for both reference sets. The insensitivity to reference states and associated partitionings favors reference states that merely reflect main structural differences for which convergence is faster. The calculations demonstrate the accuracy and robustness of FCM for large systems.

Direct thermal charging cell for converting low-grade heat to electricity.

Efficient low-grade heat recovery can help to reduce greenhouse gas emission as over 70% of primary energy input is wasted as heat, but current technologies to fulfill the heat-to-electricity conversion are still far from optimum. Here we report a direct thermal charging cell, using asymmetric electrodes of a graphene oxide/platinum nanoparticles cathode and a polyaniline anode in Fe2+/Fe3+ redox electrolyte via isothermal heating operation. When heated, the cell generates voltage via a temperature-induced pseudocapacitive effect of graphene oxide and a thermogalvanic effect of Fe2+/Fe3+, and then discharges continuously by oxidizing polyaniline and reducing Fe3+ under isothermal heating till Fe3+ depletion. The cell can be self-regenerated when cooled down. Direct thermal charging cells attain a temperature coefficient of 5.0 mV K-1 and heat-to-electricity conversion efficiency of 2.8% at 70 °C (21.4% of Carnot efficiency) and 3.52% at 90 °C (19.7% of Carnot efficiency), outperforming other thermoelectrochemical and thermoelectric systems.

Synthesis of Sea Urchin-Like NiCo2O4 via Charge-Driven Self-Assembly Strategy for High-Performance Lithium-Ion Batteries.

In this study, hydrothermal synthesis of sea urchin-like NiCo2O4 was successfully demonstrated by a versatile charge-driven self-assembly strategy using positively charged poly(diallydimethylammonium chloride) (PDDA) molecules. Physical characterizations implied that sea urchin-like microspheres of ~ 2.5 µm in size were formed by self-assembly of numerous nanoneedles with a typical dimension of ~ 100 nm in diameter. Electrochemical performance study confirmed that sea urchin-like NiCo2O4 exhibited high reversible capacity of 663 mAh g-1 after 100 cycles at current density of 100 mA g-1. Rate capability indicated that average capacities of 1085, 1048, 926, 642, 261, and 86 mAh g-1 could be achieved at 100, 200, 500, 1000, 2000, and 3000 mA g-1, respectively. The excellent electrochemical performances were ascribed to the unique micro/nanostructure of sea urchin-like NiCo2O4, tailored by positively charged PDDA molecules. The proposed strategy has great potentials in the development of binary transition metal oxides with micro/nanostructures for electrochemical energy storage applications.